PACAP STIMULATES TRANSCRIPTION OF C-FOS AND C-JUN AND ACTIVATES THE AP-1 TRANSCRIPTION FACTOR IN RAT PANCREATIC-CARCINOMA CELLS

Pituitary Adenylate Cyclase Activating Peptide (PACAP) strongly induce s proliferation of the rat pancreatic carcinoma cell line AR4-2J via i nteraction with the G-protein coupled type 1 PACAP/VIP (PV1) receptor. RT-PCR analysis revealed that this mitogenic effect of PACAP is prece ded by a rapid and transient increase of transcription of the protoonc ogene c-fos and to a lesser extent of c-jun. Transcriptional activatio n is abolished by a specific PACAP antagonist and by inhibitors of PKC and PKA. In parallel to c-fos/c-jun induction, PACAP rapidly activate s the heterodimeric transcription factor AP-1, as shown by electrophor etic mobility shift assay. These findings demonstrate that signal tran sduction of a growth-stimulating G-protein-coupled receptor involves t he c-fos/c-jun/AP-1 cascade, a pathway mainly Linked to classical grow th factor receptor tyrosine kinases. (C) 1996 Academic Press, Inc